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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

HDAC4 Gene

protein-coding GIFtS: 71
GCID: GC02M239969

histone deacetylase 4

Explore 30 diseases affiliated with
HDAC4 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Histone Deacetylase 4¹ ²		KIAA0288¹ ³
HD4¹ ² ³		EC 3.5.1.98³ ⁸
HDACA¹ ² ⁵		AHO3² ⁵
HA6116¹ ²		BDMR² ⁵
HDAC-4¹ ²		Histone Deacetylase A²
HDAC-A¹ ²

External Ids:	HGNC: 14063¹	Entrez Gene: 9759²	Ensembl: ENSG00000068024⁷	OMIM: 605314⁵	UniProtKB: P56524³

Export aliases for HDAC4 gene to outside databases

Previous GC identifers: GC02M237911 GC02M238543 GC02M239886 GC02M240182 GC02M239707 GC02M239634 GC02M231741

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for HDAC4:

Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone

acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein

encoded by this gene belongs to class II of the histone deacetylase/acuc/apha family. It possesses histone deacetylase

activity and represses transcription when tethered to a promoter. This protein does not bind DNA directly, but through

transcription factors MEF2C and MEF2D. It seems to interact in a multiprotein complex with RbAp48 and HDAC3. (provided

by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: HDAC4_HUMAN, P56524

Function: Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B,

H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional

regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large

multiprotein complexes. Involved in muscle maturation via its interaction with the myocyte enhancer factors such as

MEF2A, MEF2C and MEF2D

summary for HDAC4:

Histone Deacetylases (HDACs) are a group of enzymes closely related to sirtuins. They catalyze the removal

of acetyl groups from lysine residues in histones and non-histone proteins, resulting in transcriptional

repression. In general, they do not act autonomously but as components of large multiprotein complexes, such

as pRb-E2F and mSin3A, that mediate important transcription regulatory pathways. There are three classes of

HDACs; classes 1, 2 and 4, which are closely related Zn2+-dependent enzymes. HDACs are ubiquitously

expressed and they can exist in the nucleus or cytosol. Their subcellular localization is effected by

protein-protein interactions (for example HDAC-14.3.3 complexes are retained in the cytosol) and by the

class to which they belong (class 1 HDACs are predominantly nuclear whilst class 2 HDACs shuttle between the

nucleus and cytosol). HDACs have a role in cell growth arrest, differentiation and death and this has led to

substantial interest in HDAC inhibitors as possible antineoplastic agents.

Gene Wiki entry for HDAC4

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000002.11 NC_018913.1 NT_022173.11

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the HDAC4 gene promoter:
TBP Egr-3 AML1a p300 Cdc5 E4BP4 C/EBPalpha S8 POU2F1 POU2F1a
Other transcription factors

Browse SwitchGear Promoter luciferase reporter plasmids

Search SABiosciences Chromatin IP Primers for HDAC4

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat HDAC4

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 2q37.3 Ensembl cytogenetic band: 2q37.3 HGNC cytogenetic band: 2q37.3

HDAC4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
HDAC4 gene location

GeneLoc information about chromosome 2 GeneLoc Exon Structure

GeneLoc location for GC02M239969: view genomic region (about GC identifiers)

Start:	239,969,864 bp from pter	End:	240,323,348 bp from pter
Size:	353,485 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: HDAC4_HUMAN, P56524 (See protein sequence)

Recommended Name: Histone deacetylase 4

Size: 1084 amino acids; 119040 Da

Subunit: Interacts with HDAC7 (By similarity). Homodimer. Homodimerization via its N-terminal domain. Interacts with

MEF2C, AHRR, and NR2C1. Interacts with a 14-3-3 chaperone protein in a phosphorylation dependent manner. Interacts

with BTBD14B (By similarity). Interacts with KDM5B. Interacts with MYOCD (By similarity). Interacts with MORC2.

Interacts with ANKRA2

Subcellular location: Nucleus. Cytoplasm. Note=Shuttles between the nucleus and the cytoplasm. Upon muscle cells

differentiation, it accumulates in the nuclei of myotubes, suggesting a positive role of nuclear HDAC4 in muscle

differentiation. The export to cytoplasm depends on the interaction with a 14-3-3 chaperone protein and is due to its

phosphorylation at Ser-246, Ser-467 and Ser-632 by CaMK4 and SIK1. The nuclear localization probably depends on

sumoylation

Sequence caution: Sequence=BAA22957.2; Type=Erroneous initiation;

6/11 PDB 3D structures from and Proteopedia for HDAC4 (see all 11):

2H8N (3D)

2O94 (3D)

2VQJ (3D)

2VQM (3D)

2VQO (3D)

2VQQ (3D)

Secondary accessions: Q9UND6

Explore the universe of human proteins at neXtProt for HDAC4: NX_P56524

Post-translational modifications:

Phosphorylated by CaMK4 at Ser-246, Ser-467 and Ser-632. Phosphorylation at other residues by CaMK2D is required for

the interaction with 14-3-3. Phosphorylation at Ser-350 impairs the binding of ANKRA2 but generates a high-affinity

docking site for 14-3-3¹

Sumoylation on Lys-559 is promoted by the E3 SUMO-protein ligase RANBP2, and prevented by phosphorylation by CaMK4¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P56524

4/30 DME Specific Peptides for HDAC4 (P56524) (see all 30)

SGPSSPN

RVNHMPS

EYLAAFR

HHGNGTQ

HDAC4 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_006028.2

ENSEMBL proteins:

ENSP00000264606 ENSP00000410551 ENSP00000391226 ENSP00000405226 ENSP00000392912

ENSP00000438111 ENSP00000440481 ENSP00000443057

Reactome Protein details: P56524
Human Recombinant Protein Products for HDAC4:

	EMD Millipore Purified and/or Recombinant HDAC4 Protein
	Browse R&D Systems for human recombinant proteins
	Browse recombinant and purified proteins available from Enzo Life Sciences
	OriGene Purified Protein: HDAC4 OriGene Protein Over-expression Lysate: HDAC4 OriGene Custom Protein Services for HDAC4
	GenScript Custom Purified and Recombinant Proteins Services for HDAC4
	Novus Biologicals HDAC4 Proteins Novus Biologicals HDAC4 Lysates
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for HDAC4

Gene Ontology (GO): 5/9 cellular component terms (GO ID links to tree view) (see all 9): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000118	histone deacetylase complex	IDA	11804585
GO:0005634	nucleus	IDA	10869435
GO:0005737	cytoplasm	IDA	19281832
GO:0005829	cytosol	IEA	--
GO:0017053	transcriptional repressor complex	IDA	11804585

HDAC4 for ontologies About GeneDecksing

HDAC4 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of HDAC4
	R&D Systems Antibodies for HDAC4 (Histone Deacetylase 4/HDAC4)
	Cell Signaling Technology (CST) Antibodies for HDAC4
	OriGene Antibodies (see all 3): HDAC4 OriGene Custom Antibody Services for HDAC4
	GenScript Superior Antibodies for HDAC4
	Novus Biologicals HDAC4 Antibodies
	Abcam antibodies for HDAC4
	Uscn Antibodies for HDAC4
	ThermoFisher Antibody for HDAC4

Assay Products for HDAC4:

	EMD Millipore Kits and Assays for the Analysis of HDAC4
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for HDAC4
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for HDAC4

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

HDAC4 for domains About GeneDecksing

5 InterPro domains/families:

IPR024643 Hist_deacetylase_Gln_rich_N

IPR017320 Histone_deAcase_II_euk

IPR000286 His_deacetylse

IPR019154 Arb2_domain

IPR023801 His_deacetylse_dom

Graphical View of Domain Structure for InterPro Entry P56524

ProtoNet protein and cluster: P56524

1 Blocks protein family: IPB000286 Histone deacetylase superfamily signature

UniProtKB/Swiss-Prot: HDAC4_HUMAN, P56524

Domain: The nuclear export sequence mediates the shuttling between the nucleus and the cytoplasm

Similarity: Belongs to the histone deacetylase family. HD type 2 subfamily

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, Sirion Biotech, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, Sirion Biotech, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Molecular Function:

UniProtKB/Swiss-Prot Summary: HDAC4_HUMAN, P56524

Function: Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B,

H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional

regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large

multiprotein complexes. Involved in muscle maturation via its interaction with the myocyte enhancer factors such as

MEF2A, MEF2C and MEF2D

Catalytic activity: Hydrolysis of an N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone

Enzyme Number (IUBMB): EC 3.5.1.98¹ ²

Gene Ontology (GO): 5/18 molecular function terms (GO ID links to tree view) (see all 18): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0003677	DNA binding	--	--
GO:0003714	transcription corepressor activity	IEA	--
GO:0004407	histone deacetylase activity	IDA	10869435
GO:0005515	protein binding	IPI	11804585
GO:0008134	transcription factor binding	IPI	19071119

HDAC4 for ontologies About GeneDecksing

Phenotypes:
2 GenomeRNAi human phenotypes for HDAC4:

Increased cell death in breast

Prevent p53-dependent growth a

8 MGI mutant phenotypes (inferred from 3 alleles) (MGI details for Hdac4):

behavior/neurological	craniofacial	growth/size	integument	mortality/aging
muscle	nervous system	skeleton

HDAC4 for phenotypes About GeneDecksing

Animal Models:
Mouse knock-out Hdac4^tm1Eno for HDAC4

inGenious Targeting Laboratory - Customizable classic, inducible, and humanized mouse model solutions for HDAC4

miRNA Products:		miRTarBase miRNAs that target HDAC4: hsa-mir-1 (MIRT001053), hsa-mir-140-5p (MIRT000693), hsa-mir-22 (MIRT004035)

		OriGene 3'-UTR Clone: HDAC4 Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat HDAC4
		8/145 QIAGEN miScript miRNA Assays for microRNAs that regulate HDAC4 (see all 145):
		hsa-miR-140-5p hsa-miR-106a hsa-miR-128 hsa-miR-3653 hsa-miR-208b hsa-miR-1243 hsa-miR-3649 hsa-miR-200b

		Browse SwitchGear 3'UTR luciferase reporter plasmids

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for HDAC4 (see all 7) OriGene shRNA RFP: HDAC4 OriGene siRNA: HDAC4
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat HDAC4
		Sirion Biotech Custom design and validation of potent shRNA sequences against HDAC4

Gene Editing Products:			DNA2.0 Custom Protein Engineering Service for HDAC4
			Sirion Biotech Customized adenovirus for overexpression of HDAC4 Sirion Biotech Customized adenovirus for potent knockdown of HDAC4

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for HDAC4 (see all 2) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for HDAC4 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: HDAC4 (NM_006037)
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		DNA2.0 Custom Codon Optimized Gene Synthesis Service for HDAC4
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat HDAC4

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for HDAC4
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		Sirion Biotech Customized stable knockdown cell line services for HDAC4 Sirion Biotech Customized inducible knockdown cell line services for HDAC4 Sirion Biotech Customized stable overexpressing cell line services for HDAC4 Sirion Biotech Customized inducible overexpressing cell line services for HDAC4

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for HDAC4

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/17 super-pathways (see all 17) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Signaling by NOTCH1 t(7 9)(NOTCH1:M1580_K2555) Translocation Mutant

8/11 pathways (see all 11)
Signaling by NOTCH1 t(7 9)(NOTCH1:M1580_K2555) Translocation Mutant	1.00	Signaling by NOTCH1	1.00
Signaling by NOTCH1 PEST Domain Mutants in Cancer	1.00	Constitutive Signaling by NOTCH1 PEST Domain Mutants	0.79
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer	1.00	Signaling by NOTCH	0.77
Signaling by NOTCH1 in Cancer	1.00	Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	0.71

Immune response_Function of MEF2 in T lymphocytes

Immune response_Function of MEF2 in T lymphocytes

1.00

Immune response Function of MEF2 in T lymphocytes

0.90

Development_Ligand-dependent activation of the ESR1/AP-1 pathway

Development_Ligand-dependent activation of the ESR1/AP-1 pathway

1.00

Development Ligand-dependent activation of the ESR1/AP-1 pathway

1.00

Signal transduction Calcium signaling

Signal transduction Calcium signaling

1.00

Signal transduction_Calcium signaling

0.97

Development Role of HDAC and calcium/calmodulin-dependent kinase (CaMK) in control of skeletal myogenesis

Development Role of HDAC and calcium/calmodulin-dependent kinase (CaMK) in control of skeletal myogenesis

1.00

Development_Role of HDAC and calcium/calmodulin-dependent kinase (CaMK) in control of skeletal myogenesis

0.97

Pathway sources
See GeneCards unified pathways
Show all pathways

5 EMD Millipore Pathways for HDAC4

	Signal transduction Calcium signaling
	Immune response Function of MEF2 in T lymphocytes
	Histone modification
	Development Ligand-dependent activation of the ESR1/AP-1 pathway
	Development Role of HDAC and calcium/calmodulin-dependent kinase (CaMK) in control of skeletal myogenesis

1 Cell Signaling Technology (CST) Pathway for HDAC4

Chromatin Regulation / Acetylation

4 GeneGo (Thomson Reuters) Pathways for HDAC4

	Development Role of HDAC and calcium/calmodulin-dependent kinase (CaMK) in control of skeletal myogenesis
	Development Ligand-dependent activation of the ESR1/AP-1 pathway
	Immune response Function of MEF2 in T lymphocytes
	Signal transduction Calcium signaling

5/8 BioSystems Pathways for HDAC4 (see all 8)

	Cell cycle
	MicroRNAs in cardiomyocyte hypertrophy
	Neural Crest Differentiation
	Endochondral Ossification
	Signaling events mediated by HDAC Class III

5/13 Reactome Pathways for HDAC4 (see all 13)

	Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
	NOTCH1 Intracellular Domain Regulates Transcription
	Signaling by NOTCH
	FBXW7 Mutants and NOTCH1 in Cancer
	Signaling by NOTCH1 HD Domain Mutants in Cancer

HDAC4 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for HDAC4

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/243 Interacting proteins for HDAC4 (P56524^{1, 2, 3} ENSP00000264606⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 243)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
HIST1H4L	P62805³, ENSP00000348258⁴	I2D: score=1 STRING: ENSP00000348258
HIST1H4A	P62805³	I2D: score=1
HIST1H4B	P62805³	I2D: score=1
HIST1H4C	P62805³	I2D: score=1
HIST1H4D	P62805³	I2D: score=1

About this table

Gene Ontology (GO): 5/32 biological process terms (GO ID links to tree view) (see all 32): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000122	negative regulation of transcription from RNA polymerase II promoter	IMP	19276356
GO:0001501	skeletal system development	IEA	--
GO:0002076	osteoblast development	IEA	--
GO:0006338	chromatin remodeling	IDA	18850004
GO:0006351	transcription, DNA-dependent	IEA	--

HDAC4 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

HDAC4 for compounds About GeneDecksing

EMD Millipore small molecules for HDAC4:
Small Molecule - inhibitor

Browse drugs & compounds from Enzo Life Sciences

Compounds for HDAC4 available from Tocris Bioscience About this table

Compound	Action	CAS #
NCH 51	Histone deacetylase inhibitor	[848354-66-5]
MC 1568	Selectively inhibits HDAC class II (Iia)	[852475-26-4]
Trichostatin A	Histone deacetylase inhibitor	[58880-19-6]
KD 5170	Histone deacetylase inhibitor	[940943-37-3]
Sodium 4-Phenylbutyrate	Histone deacetylase inhibitor	[1716-12-7]

1 HMDB Compound for HDAC4 About this table

Compound	Synonyms	CAS #	PubMed Ids
Butyric acid	1-Butyrate (see all 25)	107-92-6	17258775

2 DrugBank Compounds for HDAC4 About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
2,2,2-TRIFLUORO-1-{5-[(3-PHENYL-5,6-DIHYDROIMIDAZO[1,2-A]PYRAZIN-7(8H)-YL)CARBONYL]THIOPHEN-2-YL}ETHANE-1,1-DIOL	--	--	target	--	10592235
N-hydroxy-5-[(3-phenyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)carbonyl]thiophene-2-carboxamide	--	--	target	--	10592235

10 Novoseek chemical compound relationships for HDAC4 gene About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
trapoxin	78	1	11134513 (1)
lysine	43.1	2	16166628 (1), 19251700 (1)
threonine	35.3	3	11114188 (1)
serine	29.1	5	15205465 (1), 11114188 (1), 11390982 (1)
butyrate	20	1	20383178 (1)
calcium	16.9	21	12663674 (3), 10825153 (3), 18332106 (2), 16767219 (2) (see all 11)
alanine	16.7	3	20188095 (1), 18045992 (1)
zinc	14.5	2	18614528 (1), 19355988 (1)
retinoid	7.48	1	17383980 (1)
glutamate	0	1	15205465 (1)

Search CenterWatch for drugs/clinical trials and news about HDAC4

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, Sirion Biotech, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for HDAC4 gene:

NM_006037.3

Unigene Cluster for HDAC4:

Histone deacetylase 4

Hs.20516 [show with all ESTs]

Unigene Representative Sequence: NM_006037

18 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000345617(uc010fyy.3 uc002vyk.4) ENST00000430200 ENST00000494800

ENST00000487617 ENST00000463007(uc010fyz.1) ENST00000495497 ENST00000493582(uc010fza.2)

ENST00000535493(uc010zoa.1) ENST00000460235 ENST00000461113(uc010fzb.1)

ENST00000445704 ENST00000553145 ENST00000454542 ENST00000446876 ENST00000496347

ENST00000544989 ENST00000543185 ENST00000541256(uc010znz.1)

miRNA Products:		OriGene 3'-UTR Clone: HDAC4 Browse OriGene MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat HDAC4
		8/145 QIAGEN miScript miRNA Assays for microRNAs that regulate HDAC4 (see all 145):
		hsa-miR-140-5p hsa-miR-106a hsa-miR-128 hsa-miR-3653 hsa-miR-208b hsa-miR-1243 hsa-miR-3649 hsa-miR-200b

		Browse SwitchGear 3'UTR luciferase reporter plasmids

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for HDAC4 (see all 7) OriGene shRNA RFP: HDAC4 OriGene siRNA: HDAC4
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat HDAC4
		Sirion Biotech Custom design and validation of potent shRNA sequences against HDAC4

Clone Products:		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for HDAC4 (see all 2) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for HDAC4 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: HDAC4 (NM_006037)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for HDAC4
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat HDAC4

Primer Products:		OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for HDAC4 Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay in human, mouse, rat HDAC4
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat HDAC4
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat HDAC4

Additional cDNA sequence:

AB006626.2 AF070607.1 AF132607.1 AK302719.1 AK303368.1 AK303467.1 AK303617.1 AK308791.1

AK310488.1 AK310603.1 AK311582.1 BC039904.1

14 DOTS entries:

DT.315082 DT.95176516 DT.97794529 DT.92056881 DT.120978132 DT.91785600 DT.95189639 DT.95365884

DT.100831917 DT.95131879 DT.95352125 DT.95365888 DT.99969378 DT.100728217

24/115 AceView cDNA sequences (see all 115):

AW072681 AI491868 AI823559 AB006626 AI801599 CR607186 AF132607 AJ707294

BC039904 BF448234 AI198969 BM676799 AA350265 BG574696 AI186037 CR625452

AL043738 AI342576 NM_006037 AI498343 AW084671 BV200078 AA948549 AA987969

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

HDAC4 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: ACATTTGCAG

About this image

HDAC4 expression in embryonic tissues and stem cells
Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

3 LifeMap In Vivo Development Anatomical Compartments/Cells

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Bone

Autopod Growth Plate

Prehypertrophic Chondrocytes

Bone, Cartilage

Bone

Stylopod Growth Plate

Prehypertrophic Chondrocytes

Bone, Cartilage

Bone

Zeugopod Growth Plate

Prehypertrophic Chondrocytes

Bone, Cartilage

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

See HDAC4 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for HDAC4

SOURCE GeneReport for Unigene cluster: Hs.20516

UniProtKB/Swiss-Prot: HDAC4_HUMAN, P56524

Tissue specificity: Ubiquitous

SABiosciences Expression via Pathway-Focused PCR Arrays including HDAC4 (see all 6):

Neurogenesis in human mouse rat

Epigenetic Chromatin Modification Enzymes in human mouse rat

Cancer Drug Targets in human mouse rat

Nuclear Receptors & Coregulators in human mouse rat

Inflammatory Response & Autoimmunity 384HT in human mouse rat

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In Situ
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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of eukaryotes.

Orthologs for HDAC4 gene from 7/27 species (see all 27) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	HDAC4¹	histone deacetylase 4	81.56(n) 91.1(a)		374207 NM_204313.1 NP_989644.1
lizard (Anolis carolinensis)	Reptilia	HDAC4⁶	--	87(a)	1 ↔ 1	1(118479128-118562758)
zebrafish (Danio rerio)	Actinopterygii	wufc56f08²	wufc56f08	82.59(n)		325153 57051044
fruit fly (Drosophila melanogaster)	Insecta	HDAC4^{1 , 3}	histone deacetylase³ CG1770-PB¹	57(a)³ 50.31(n)¹ 41.11(a)¹		11E8³ 32278¹ NM_132640.4¹ NP_572868.3¹
worm (Caenorhabditis elegans)	Secernentea	hda-4³	Expression: mu_bod, hypodermal, seam cells, amphid more	50(a) (best of 2)		X(16771247-16775220) --
thale cress (Arabidopsis thaliana)	eudicotyledons	hda14⁶ HDA08⁶	histone deacetylase 8	25(a) 21(a)	possible ortholog possible ortholog	4(16102595-16105493) 1(2672451-2674628)
rice (Oryza sativa)	Liliopsida	Os.21399²	Oryza sativa (japonica cultivar-group) putative histone more	72.29(n)		AK111557.1

ENSEMBL Gene Tree for HDAC4 (if available)
TreeFam Gene Tree for HDAC4 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for HDAC4 gene

HDAC9² HDAC6² HDAC5² HDAC7² HDAC10²

8 SIMAP similar genes for HDAC4 using alignment to 9 protein entries: HDAC4_HUMAN (see all proteins):

MGC16025 HDAC9 KIAA0600 HDAC7 HDAC5 DKFZp779K1053

DKFZp586I031 HDAC6

HDAC4 for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 2 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs62190764^1,2	C	--	231818375(+)	`CATTCC/TGGTGT`	1	--	int¹		1		WA	2
rs73000120^1,2	C	--	231818554(+)	`TGGCCG/ACGCAT`	1	--	int¹		2		CSA NA	122
rs34996676^1,2	C	--	231821834(+)	`TGGGT-/GGATCA`	1	--	int¹		1		NA	2
rs73104762^1,2	C	--	232040246(+)	`ACATTC/GAACCA`	1	--	ds500¹		2		WA	120
rs10179405^1,2	C	--	232041099(+)	`CCTATC/TGAGAG`	1	--	nc-transcript-variant		0	--	--	--	--
rs74003944^1,2	C	--	232041591(+)	`CCTTAA/TCCACA`	1	--	nc-transcript-variant		3		WA NA	240
rs59968472^1,2		--	232042277(+)	`AGCCAC/GGCAGG`	1	--	us2k¹		0	--	--	--	--
rs76087356^1,2	F	--	232042568(+)	`TTCCAG/ACAATG`	1	--	us2k¹		1		EA	120
rs80324222^1,2	C	--	232042598(+)	`GTGCAC/TCAGCT`	1	--	us2k¹		1		WA	2
rs11680390^1,2	H	--	232043417(+)	`AATGGT/GTATTA`	1	--	us2k¹		4		NS EA	418

HapMap Linkage Disequilibrium report for HDAC4 (239969864 - 240219864 bp, first 250kb of HDAC4)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 11 variations for HDAC4
5 CNVs: 4330 9443 68276 68275 35797
6 Indels: 68274 45973 42926 90382 79061 26615
Human Gene Mutation Database (HGMD): HDAC4

SABiosciences Cancer Mutation PCR Assays

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

HDAC4 for disorders           About GeneDecksing

OMIM gene information: 605314
OMIM disorders: 600430
UniProtKB/Swiss-Prot: HDAC4_HUMAN, P56524

Defects in HDAC4 are the cause of brachydactyly-mental retardation syndrome (BDMR) [MIM:600430]. A syndrome

resembling the physical anomalies found in Albright hereditary osteodystrophy. Common features are mild facial

dysmorphism, congenital heart defects, distinct brachydactyly type E, mental retardation, developmental delay,

seizures, autism spectrum disorder, and stocky build. Soft tissue ossification is absent, and there are no

abnormalities in parathyroid hormone or calcium metabolism

20/30 diseases for HDAC4 (see all 30): About MalaCards

brachydacytly-mental retardation syndrome brachydactyly-mental retardation syndrome albright's hereditary osteodystrophy mental retardation syndrome

neuronal intranuclear inclusion disease brachydactyly type e brachydactyly muscle hypertrophy

acute myeloid leukemia herpes simplex myeloid leukemia rheumatoid arthritis

neurodegenerative disease chondrosarcoma hepatocellular carcinoma leukemia

colon cancer arthritis lung carcinoma osteosarcoma

1 disease from the University of Copenhagen DISEASES database for HDAC4:

Brachydactyly

5 Novoseek disease relationships for HDAC4 gene About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
cardiac hypertrophy	34.8	3	17179159 (2), 17038545 (1)
hypertrophy	29.2	6	19716643 (2), 15537533 (1), 16767219 (1), 19704004 (1) (see all 5)
cancer	16.5	11	18850004 (2), 19888759 (2), 17363583 (1), 19649663 (1) (see all 8)
tumors	15.4	14	19622775 (6), 18850004 (1), 18227124 (1), 19956841 (1) (see all 8)
leukemia	13.2	3	16409557 (1), 20393011 (1)

Human Genome Epidemiology (HuGE) Navigator: HDAC4 (6 documents)

Export disorders for HDAC4 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for HDAC4 gene, integrated from 9 sources (see all 263):
(articles sorted by number of sources associating them with HDAC4)

Utopia: connect your pdf to the dynamic
world of online information

Three proteins define a class of human histone deacetylases related to yeast Hda1p. (PubMed id 10220385)^{1, 2, 3, 9} Grozinger C.M....Schreiber S.L. (1999)
HDAC4, a human histone deacetylase related to yeast HDA1, is a transcriptional corepressor. (PubMed id 10523670)^{1, 2, 9} Wang A.H.... Yang X.-J. (1999)
Nuclear calcium/calmodulin-dependent protein kinase IIdelta preferentially transmits signals to histone deacetylase 4 in cardiac cells. (PubMed id 17179159)^{1, 2, 9} Little G.H....Poizat C. (2007)
The modular nature of histone deacetylase HDAC4 confers phosphorylation-dependent intracellular trafficking. (PubMed id 11470791)^{1, 2, 9} Zhao X.... Yao T.-P. (2001)
Regulation of histone deacetylase 4 by binding of 14-3-3 proteins. (PubMed id 10958686)^{1, 2, 9} Wang A.H.... Yang X.-J. (2000)
A new family of human histone deacetylases related to Saccharomyces cerevisiae HDA1p. (PubMed id 10206986)^{1, 3, 9} Fischle W....Verdin E. (1999)
HDAC4 deacetylase associates with and represses the MEF2 transcription factor. (PubMed id 10487761)^{1, 2, 9} Miska E.A....Kouzarides T. (1999)
Involvement of histone deacetylation in MORC2-mediate d down-regulation of carbonic anhydrase IX. (PubMed id 20110259)^{1, 2, 9} Shao Y....Li F. (2010)
Sequence-specific recognition of a PxLPxI/L motif by a n ankyrin repeat tumbler lock. (PubMed id 22649097)^{1, 2} Xu C....Min J. (2012)
Haploinsufficiency of HDAC4 causes brachydactyly ment al retardation syndrome, with brachydactyly type E, developmental delays, and b ehavioral problems. (PubMed id 20691407)^{1, 2} Williams S.R....Elsea S.H. (2010)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 9759	HGNC: 14063	AceView: HDAC4	Ensembl:ENSG00000068024	euGenes: HUgn9759
ECgene: HDAC4	H-InvDB: HDAC4

(According to HUGE)
About This Section

HUGE: KIAA0288

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for HDAC4	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for HDAC4	Genetics and Cytogenetics in Oncology and Haematology

Intellectual Property for HDAC4 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

About This Section

Patent Information for HDAC4 gene:
Search GeneIP for patents involving HDAC4

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Uscn, Thermo Fisher Scientific, Gene Editing from DNA2.0 and Sirion Biotech, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript, LifeMap BioReagents, and Sirion Biotech, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences, In Situ Hybridization Assays from
Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory)
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histone deacetylase 4

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histone deacetylase 4

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